D-penicillamine and beta-aminopropionitrile effects on experimental filtering surgery.

We studied the effect of two compounds, beta-aminopropionitrile (BAPN) and D-penicillamine on the success of experimental glaucoma filtering surgery in cynomolgus monkeys. All animals had laser-induced glaucoma and underwent punch sclerectomy operations. Eyes treated with BAPN or D-penicillamine maintained successful filtration for at least 3 days longer than nondrug-treated controls. This effect, while statistically significant (P less than 0.05), was temporary. The lack of more substantial improvement in prolonging filtering patency may have resulted from an inadequate effective drug concentration. Alternatively, these drugs may have limited potency because their action on new collagen synthesis affects only a minor component of the healing process that causes filter failure.

Dexamethasone, D-penicillamine, and glaucoma filter surgery in rabbits.

A study was made in rabbits of the effect of topical dexamethasone ointment, .05%, and either subconjunctival or intraperitoneal D-penicillamine on the duration of function of glaucoma filtering surgery. The drugs were tested alone and in combination. Intraperitoneal D-penicillamine was not effective, either alone or combined with topical dexamethasone. Topical dexamethasone ointment alone and subconjunctival D-penicillamine alone significantly prolonged the duration of function of the filter surgery; however, when combined, no additional effect was observed. It was concluded that the institution of therapy with both drugs immediately after glaucoma filtering surgery was not the optimal temporal sequence for combining the two modes of therapy.

The effects of D-penicillamine and daunorubicin on conjunctival fibroblast proliferation and collagen synthesis.

Two drugs, D-penicillamine and daunorubicin, were tested for their effect on proliferation and collagen synthesis of cultured conjunctival fibroblasts. This cell type is likely responsible for scar formation and ultimate filter surgery failure in glaucoma patients. Both drugs were antiproliferative; however, D-penicillamine required 2000 times the concentration of daunorubicin to achieve a similar degree of inhibition. D-penicillamine had a more consistent effect on intracellular collagen synthesis than daunorubicin at the doses tested. In contrast, at concentrations of daunorubicin where all proliferation ceased, intracellular production and extracellular transport of collagen were maintained.

Assessment of diclofenac on herpes keratitis in rabbit eyes.

Topical diclofenac sodium is a non-steroidal anti-inflammatory drug that is being developed for use in the control of postoperative and medical inflammation. A comparison was made of 0.1% diclofenac with 1% prednisolone sodium phosphate, 0.03% flurbiprofen, and a vehicle placebo in rabbit eyes with acute herpetic keratitis in a double-masked study. Maximum corneal epithelial involvement was observed in each group on day 6 postinoculation, and in eyes subsequently treated with prednisolone, the corneal epithelial involvement appeared to be more severe and to resolve more slowly. Conjunctivitis and corneal clouding peaked on days 6 to 7 for all treatment groups and remained most severe in the placebo-treated eyes, followed closely by those treated with prednisolone. The duration of virus shedding was the same for placebo-, flurbiprofen-, and diclofenac-treated groups (50% or more were virus negative by day 10 or 11). Only prednisolone-treated eyes had an extended period of virus shedding, and the rabbit mortality rate in this group was slightly higher. It thus appears that topical diclofenac does not exacerbate acute herpes keratitis; diclofenac-treated eyes displayed less or at least no more severe disease than did the eyes treated with the other anti-inflammatory agents tested, and shedding of virus into tears was not prolonged.

Cellular proliferation after experimental glaucoma filtration surgery.

We used light microscopic autoradiography to determine the time course of cellular incorporation of tritiated thymidine (a correlate of cell division) following glaucoma filtration surgery in seven eyes of four cynomolgus monkeys with experimental glaucoma. Incorporation of tritiated thymidine was detected as early as 24 hours postoperatively. Peak incorporation occurred five days postoperatively and had returned to baseline levels by day 11. Cells incorporating tritiated thymidine included keratocytes, episcleral cells, corneal and capillary endothelial cells, and conjunctival and corneal epithelial cells. Transmission electron microscopy was correlated with the autoradiographic results to demonstrate that fibroblasts were dividing on the corneoscleral margin. These findings have potential clinical implications for the use of antiproliferative agents after filtration surgery.

Extracapsular cataract extraction and posterior chamber lens implantation in eyes with preexisting glaucoma.

Fifty eyes of 40 patients with glaucoma underwent extracapsular cataract extraction with posterior chamber lens implantation. Their visual results and early postoperative complications were compared with those of eyes in an age-matched group of patients without glaucoma after the same procedure. Substantial increases in early postoperative intraocular pressure (IOP) occurred in 62% of the glaucomatous eyes and in only 10% of the normal eyes. The level of best visual acuity was slightly worse (20/40) on average in the glaucomatous eyes than in the nonglaucomatous eyes (20/25). At six months after surgery, 82.5% of the nonfiltered glaucomatous eyes needed the same number of or additional glaucoma medications to maintain an IOP of less than 20 mm Hg. Ten of the glaucomatous eyes underwent trabeculectomy along with cataract surgery due to inadequate IOP control while the patient was receiving maximum medical therapy. Control was substantially improved, with 100% of these patients receiving the same number of or fewer medications at six months. By one year, only 30% of these patients required the same number of medications postoperatively as preoperatively, but all had IOP control.

Topical nonsteroidal agents and corneal wound healing.

The effects on corneal wound healing of two topical nonsteroidal anti-inflammatory agents, flurbiprofen sodium (0.03%) and diclofenac sodium (0.1%), and the topical corticosteroid, prednisolone sodium phosphate (1%), were evaluated in masked, controlled rabbit studies. Healing of epithelial scrape wounds was significantly retarded in all three treatment groups for the first 3 days after wounding. There was no difference in the epithelial healing rate between the two nonsteroidal or corticosteroid treatment groups. Clinical grading of epithelial quality, conjunctival hyperemia, keratitis, stromal edema, and corneal haze were similar in all groups. There was a significant early decrease in the iritis score in the diclofenac treatment group. The strength of 2-mm central penetrating corneal trephination wounds and the collagen content of these wounds were similar in all groups. Both the topical nonsteroidal anti-inflammatory agents and the corticosteroid used in the preparations and dosages investigated in this study decreased early epithelialization of scrape wounds but had no apparent effect on corneal stromal healing. No toxic effects of the various drugs were found.

Subscleral Scheie operation for advanced glaucoma.

The subscleral Scheie procedure is most effective in advanced glaucoma patients with IOP of 35 mm Hg or more and in those patients in need of a secondary or tertiary procedure. The surgical technique is described.